An oxygen-insensitive and minimally invasive polymeric microneedle sensor for continuous and wide-range transdermal glucose monitoring.

Despite significant advances in diabetes management, particularly with the introduction of the most recent continuous glucose monitoring devices (CGMDs) that can monitor glucose actively in the transdermal interstitial fluid (ISF) in vivo, CGMDs still have significant disadvantages in terms of accuracy, low interference effect, precision, and stability. This is mostly because they detect hydrogen peroxide at higher potentials and require an oxygen-rich environment. First in its class, we developed an oxygen-insensitive polymeric glucose microneedle (MN) that was functionalized using a new electron-transfer mediator, 3-(3'-phenylimino)-3H-phenothiazinesulfonic acid-based enzyme cocktail for the NAD-GDH system. The inclusion of reduced graphene oxide aided in the absorption of the cocktail via the π-π interaction and enhanced the conductivity and sensor performance. The MN exhibited a dynamic linear range (1-30 mM) with a low detection limit of 26 μM, high sensitivity (18.05 μAmM cm), stability (up to 7 days), high selectivity (due to a low oxidation potential of 0.15 V), and a fast response time (∼3 s). In vivo, deployment of the MN in a rabbit model demonstrated that the ISF glucose concentrations measured with the MN for up to 24 h correlate very well with the blood glucose concentrations measured with a commercial glucometer.